In 1972 we presented evidence for the existence of an insulin sensitive center in the central nervous system (CNS). Selective regional insulination through the carotid artery in anesthetized rats resulted in reduction of systemic blood sugar in healthy as well as experimental diabetic animals, presumably by inhibition of hepatic glucose production. The objectives of the current research project are: 1) to elucidate the hormonal or neural pathway(s) which transmit the impulses from the insulin sensitive CNS glucoregulator receptor center to regulate hepatic glucose metabolism, 2) to localize the center within the CNS, 3) to identify the mechanism of action of the insulin sensitive chemoreceptors within the evidenced glucoregulator center, 4) to study the behavior of the chemoreceptor(s) in experimental conditions resembling human disease states, such as obesity, hyperinsulinemia, growth hormone excess and diabetes mellitus, 5) to clarify the mode of action of the receptor within the CNS glucoregulator center, 6) to study the pathway through which the signal to lower the blood sugar reaches the effector organ, 7) to perform preliminary studies on morphological localization of the insulin sensitive glucoregulator receptor. It is hoped that these studies will contribute toward the understanding of a previously unsuspected action of insulin on carbohydrate metabolism, mediated through the CNS. As this is an extremely sensitive, very rapid action, its investigation may be of importance far beyond academic interest, inasmuch as it may yield clues to the initial metabolic errors which lead to important disease states, such as obesity, hyperinsulinism, and diabetes mellitus.